The objective of the project is to determine what factors govern the acyl chain length specificity in different mammalian lipogenic systems. The enzymes involved in fatty acid synthesis are integrated into a multienzyme complex. The multienzymes from all mammalian tissues, in isolation, synthesize predominantly C16 fatty acid. We have been able to isolate a peptide, with thioesterase activity, from the multienzyme complexes of rat liver and lactating mammary gland. This enzyme is responsible for termination of growth of the acyl chain on the multienzyme complexes. The thioesterase is highly specific for C16 thioesters, so its specificity may acount for the chain length of fatty acids synthesized by the isolated multienzymes. We have also isolated a second thioesterase, not part of a multienzyme, from lactating rat mammary gland. This enzyme has a broad specificity for both short and long chain thioesters. We are investigating the possibility that in lactating mammary gland the second thioesterase may be able to interact with the multienzyme in such a way as to modify the product specificity of the complex. Such a phenomenon would represent a novel tissue specific control mechanism by which the lactating mammary gland is able to synthesize the short chain fatty acids characteristic of milk fat. BIBLIOGRAPHIC REFERENCES: "Specific Modification of Fatty Acid Synthetase from Lactating Rat Mammary Gland by Chymotrypsin and Trypsin," by Elisabetta Agradi, Louis Libertini and Sturart Smith. Biochem. Biophys. Res. Commun., 1976. In press. "Specific Release of the Thioesterase Component of the Fatty Acid Synthetase Complex by Limited Trypsinization," by Stuart Smith, Elisabetta Agradi, Louis Libertini and K. N. Dileepan. Proc. Nat. Acad. Sci. (U.S.A.) 1976. In press.